All publications herein are incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. The following description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
One gastrointestinal disorder is short bowel syndrome (SBS), also referred to as small intestine insufficiency. SBS is a serious, often life-threatening, medical problem resulting in severe diarrhea and nutritional deprivation. Injury or trauma may cause short bowel syndrome; for example, surgical removal of a large portion of the small intestine. The removal may result in the lack of surface area in the remaining bowel to absorb enough nutrients from food. Short bowel syndrome may also be caused by the small intestine's loss of absorptive function due to diseases; for example, Crohn's disease and cancer. Though rare, short bowel syndrome may be congenital and is often referred to as Congenital Short Bowel Syndrome.
Other symptoms of short bowel syndrome include, but are not limited to abdominal pain, steatorrhoea, greasy stools, edema, weight loss, and fatigue. The symptoms result from a lack of absorptive surface and loss of the braking mechanisms controlling the proximal gut. One of the missing, distally produced, peptides that control the proximal gut is glucagon-like peptide-1 (GLP-1). Complications due to short bowel syndrome include weight loss, malnutrition, weakened bones, gallstones, bacterial overgrowth, metabolic acidosis and kidney stones.
Currently available treatments for short bowel syndrome aim to relieve its symptoms. A high-calorie and low-residue diet may be prescribed. Medications attempt to lengthen the time the nutrients are available in the intestine for absorption. In instances wherein normal feeding is not delivering enough nutrients, parenteral nutrition may be necessary. Surgery, such as intestinal lengthening or tapering, may be performed.
Currently, there is no cure for short bowel syndrome and treatment options are not completely effective for all patients. Thus, there is a need in the art for alternative or improved methods and compositions to treat short bowel syndrome.
Other gastrointestinal disorders include spastic or hyperactive esophageal motor disorders which may limit the delivery of food and liquid, as well as cause painful symptoms. Examples of spastic or hyperactive esophageal motor disorders include, but are not limited to, esophageal spasms, nutcracker esophagus and achalasia.
Esophageal spasms are uncoordinated series of muscle contractions that prevent the proper traveling of food into the stomach. Some signs and symptoms of esophageal spasms include chest pain, difficulty swallowing, painful swallowing, a sensation that an object is stuck in the throat, regurgitation, and heartburn. Short term treatment of esophageal spasms may involve the use of medications to relax the esophageal muscles. Long term treatment of esophageal spasms may include management of any contributing health condition (e.g., gastroesophageal reflux disease (“GERD”)), medications, and alteration of eating habits.
Nutcracker esophagus is an abnormality wherein swallowing contractions are too powerful. Symptoms of nutcracker esophagus include chest pain, dsyphagia, and heartburn. Treatment options for nutcracker esophagus include anti-reflux therapy to treat an underlying cause (e.g., GERD), use of medications such as nitrates or calcium channel blockers to relax the esophageal and stomach muscles, and use of tricyclic antidepressants to lower the pain sensation.
Achalasia is an esophageal disorder wherein the esophagus is less able to move food towards the stomach and the muscle from the esophagus to the stomach does not relax as much as it needs to be during swallowing. Symptoms of achalasia include difficulty swallowing liquids and solids, regurgitation of food, chest pain, weight loss, heart burn and cough. Current treatment for achalasia seeks to reduce the pressure at the lower esophageal sphincter; for example, widening of the lower esophageal sphincter or injecting the lower esophageal sphincter with botulimun toxin to paralyze it and prevent spasms. Long-acting nitrates and calcium channel blockers may also be used to lower the pressure of the lower esophageal sphincter. Complications of achalasia may include perforation of the esophagus, reflux, and aspiration of food into the lungs.
However, anti-reflux medications only reduce a risk factor for these conditions; medications to relax the muscles only provide relief to some patients and their effectiveness overall is not very good; and the use of antidepressants only treats the associated pain, rather than the abnormalities themselves. Thus, there exists a need in the art for alternative and/or additional treatments for spastic or hyperactive esophageal motor disorders.